Evaluation of Circ-Nrf2s Expression on Oxidative Stress Condition and Prediction Its Interaction with mi-RNAs and Proteins

Abstract

Background: Circular RNAs (Circ RNA) are a large class of non-coding RNAs which particularlystable RNAs and mostly originate from gene exons in animals. circRNAs are extremely abundantin the mammalian brains. They play role in the biological function and development of neurons.Nrf2 (nuclear factor erythroid 2–related factor 2) is a transcription factor that regulates cellularantioxidants and improves hippocampal synaptic plasticity, learning and memory. The aim ofthis study is the evaluation of Nrf2’s circRNA expression in the hippocampus of rats duringoxidative stress and the prediction of their function by bioinformatic tools. Methods: After evaluation of Nrf2’s circRNA prediction from circAtlas by BLAST, 3 out of 4sequences with high homology were selected and circ-Nrf2s expression was evaluated by qPCR,the interaction with micro RNAs and proteins was evaluated by miRDB, TargetScan, catRAPIDand HDOCK web server. Except control group, two groups of rats were treated with H2O2 (1%and 5%) then rats were sacrificed and hippocampal tissue was separated. qPCR was performedfor Nrf2 pathway gene expression and Nrf2 circRNAs. Then Circ-Nrf2-miRNA and 2circ-Nrf2-protein interaction were evaluated. Results: The most important circRNA that origin from Nrf2 is circ-Nrf2-1. Circ-Nrf2-1downregulates in oxidative stress and upregulates in 5% of H2O2 compared to 1%. However,linear Nrf2 was upregulated in both 1% and 5% H2O2. Circ-Nrf2-1 can bind to several miRNAsincluding miR-144-3p, miR-148a-5p, miR-155-5p. It also interacts with Celf1 which plays a rolein oxidative stress. Conclusion: According to results, it is plausible to suggest that circNrf2 may play a regulatoryrole in modulating oxidative stress.